Department of Animal Science, Chungbuk National University, Cheongju, South Korea.
FASEB J. 2019 Jul;33(7):7882-7895. doi: 10.1096/fj.201802473R. Epub 2019 Mar 21.
Phosphatase and tensin homolog-induced kinase 1 (PINK1) on the outer membranes of impaired mitochondria promotes mitophagy and regulates mitochondrial morphology. Mammalian oocytes and early embryos are mitochondria rich, but mitochondrial dynamics during preimplantation embryo development is not well-studied. To investigate whether PINK1 is required for mitochondrial dynamics in porcine preimplantation embryos, gene knockdown and inhibitors were used, and mitochondrial dynamics were observed by transmission electron microscopy. knockdown significantly impaired blastocyst formation and quality, induced mitochondrial elongation and swelling, and reduced mitochondrial DNA copy number. knockdown-induced mitochondrial elongation caused mitochondrial dysfunction, oxidative stress, and ATP deficiency, significantly increasing autophagy and apoptosis. Profission dynamin-related protein 1 overexpression prevented knockdown-induced impairment of embryo development, mitochondrial elongation, and dysfunction. Thus, PINK1 promotes mitochondrial fission in porcine preimplantation embryos.-Niu, Y.-J., Nie, Z.-W., Shin, K.-T., Zhou, W., Cui, X.-S. PINK1 regulates mitochondrial morphology promoting mitochondrial fission in porcine preimplantation embryos.
磷酸酶和张力蛋白同源物诱导激酶 1(PINK1)在受损线粒体的外膜上促进线粒体自噬并调节线粒体形态。哺乳动物卵母细胞和早期胚胎富含线粒体,但在植入前胚胎发育过程中线粒体动力学尚未得到很好的研究。为了研究 PINK1 是否需要猪植入前胚胎中线粒体动力学,使用基因敲低和抑制剂,并通过透射电子显微镜观察线粒体动力学。结果表明, 敲低显著损害囊胚形成和质量,诱导线粒体伸长和肿胀,并降低线粒体 DNA 拷贝数。 敲低诱导的线粒体伸长导致线粒体功能障碍、氧化应激和 ATP 缺乏,显著增加自噬和细胞凋亡。分裂 dynamin 相关蛋白 1 的过表达可防止 敲低诱导的胚胎发育、线粒体伸长和功能障碍。因此,PINK1 促进猪植入前胚胎中线粒体分裂。